PB2251: SOMETIMES IT’S ZEBRAS: SUCCESSFUL TREATMENT OF ERYTHROPOIETIC PROTOPORPHYRIA POST PRIMARY MYELOFIBROSIS WITH GIVOSIRAN - A CASE REPORT
Authors: Alina Catana, Geanina Mera, Cristina Popa
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: A 66 year old female patient presented in January 2022 with severe weight loss of 10 kg (down to 42 kg); severe polyneuropathy-type pains progressing in the lower limbs, intense headaches requiring Metamizole every 2 hours, abdominal-pelvic pain, asthenia, adynamia, urine dark in color and sometimes reddish, back pain, insomnia, and constipation starting in 2018 but in December 2021 she went to the hospital where severe anemia was discovered without an obvious cause, and injectable iron, B12, folic acid, and RBC were administered. After the administration of iron, the pain in the lower limbs intensified. Aims: Accurate diagnosis and specific treatment. Methods: Laboratory tests – CBC, Folic acid, Vitamin B12, Peripheral blood smear, Bone marrow biopsy and aspiration, JAK2 V617F, MPL, CALR Upper endoscopy, CT Scan, EMG Results:20.01.2022 Hematology Sibiu: •Biologic: Severe anemia Hb = 7 g/dl; L = 4620/mm3; T = 93000/mm3; normal folic acid, vit b12, increased ferritin; EM: leucoerythroblastic picture •Bone marrow aspirate: white puncture; Bone marrow histopathology: myelofibrosis; Molecular biology: JAK2 V617F, MPL, CALRETICULIN negative. Upper endoscopy: gastritis; Colonoscopy: no changes; •CT scan: homogenous splenomegaly 14.5 cm; dilated endometrial cavity with parafluid-tissue content; alternation of osteocondensation with osteolysis; 2 units of blood transfusion; •COVID on the ward - discharge; Mild COVID infection in February 2022. 1.03.2022 Minimal vaginal bleeding, moderate anemia Hb = 8 G/DL; leucoerythroblastic picture: FL: 1/2/5/48/1/1/32/10 and 1% Bl and 1% ebl; ESR>120 mm/h; Gynecological consultation: hematometra; biopsy curettage: severe dysplastic changes/squamous cell carcinoma in situ. Total hysterectomy with bilateral annexectomy: foci of squamous cell carcinoma in situ without associated microinvasion. 06.2022: EMG: Moderate to severe axonal degeneration, asymmetric sensory-motor, in a patient with worsening gait disorders and musculoskeletal and muscular pain in the lower limbs, along with significant weight loss; The patient lived in Copsa Mica, an area endemic for lead poisoning - serological analyses were indicated with suspected lead poisoning. Normal levels of C-peptide and insulin ruled out insulinoma - the patient experienced frequent hypoglycemia. Psychiatric consultation: Moderate depressive episode. Urinary porphobilinogen: 7.38mg/24h (0.10-1.70) Blood Pb: 11.20ug/dL (<=24.90) Urinary Pb: 47.40ug/dL (<50) Delta ALA: 3.62mg/L (<4.50) Genetic testing for porphyria: The following variant was found in heterozygous state: FECH (NM_000140.5): c.362A>G (p.(Glu121Gly)). Summary/Conclusion Off-label treatment with Givosiran once a month was initiated in November 2022, with a spectacular evolution after the initiation of treatment, with the disappearance of limb pain and headaches, without analgesic treatment, and 9 kg weight gain. “I feel human again and a mother to my children.” Genetic advice: Porphyria testing: 2 out of three children are asymptomatic carriers of the FECH gene, the third child with test results pending. She avoids substances and medications that trigger porphyria attacks. Hereditary protoporphyria - probably the appearance of primary myelofibrosis with aggressive evolution and carcinoma in situ at the level of the cervix to explain the extremely expressive/aggressive phenotype of the patient. Some cases of porphyria associated with neoplasms and some cases of porphyria associated with primary myelofibrosis with evolution towards acute leukemia. It is a unique case with 2 malignancies associated with a probably recessive transmission porphyria but with an aggressive phenotype. Keywords: Myeloproliferative disorder, Myeloid malignancies